Evaluating the Safety of and Adherence to a Vaginal Matrix Ring Containing Dapivirine and Oral Emtricitabine/Tenofovir Disoproxil Fumarate in an Adolescent and Young Adult Female Population

• ClinicalTrials.gov Identifier: NCT03593655
• Recruitment Status: Recruiting
• First Posted: July 20, 2018
• Last Update Posted: November 5, 2019
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety of and adherence to a vaginal matrix ring (VR) containing dapivirine and oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in adolescent and young adult females.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Device: Dapivirine vaginal ring; Drug: FTC/TDF	Phase 2

Detailed Description:

This study will evaluate the safety of and adherence to a vaginal matrix ring (VR) containing dapivirine and oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in adolescent and young adult females.

The study will enroll healthy, HIV-uninfected adolescent and young adult females between 16 and 21 years of age. Participants will be randomized to one of two sequences of one VR containing 25 mg of dapivirine to be inserted monthly for 24 weeks and one 200 mg FTC/300 mg TDF oral tablet taken daily for 24 weeks. After completing the randomized sequence of two study product use periods, participants will then select between the two study products to use in the final 24 weeks of the trial. Participants will be able to choose either or neither study product during the third product use period. The study includes approximately 76 weeks of follow-up per participant.

Participants will attend monthly study visits, which may include behavioral assessments/counseling; physical and pelvic examinations; and blood, urine, and pelvic sample collection.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 2a Crossover Trial Evaluating the Safety of and Adherence to a Vaginal Matrix Ring Containing Dapivirine and Oral Emtricitabine/Tenofovir Disoproxil Fumarate in an Adolescent and Young Adult Female Population
• Actual Study Start Date: January 14, 2019
• Estimated Primary Completion Date: November 30, 2021
• Estimated Study Completion Date: November 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sequence A: Dapivirine vaginal ring + FTC/TDF; Participants will receive one 25 mg dapivirine vaginal ring inserted vaginally each month for 24 weeks, followed by one FTC/TDF oral tablet taken by mouth daily for 24 weeks, followed by participant's choice of either or neither study product for 24 weeks.	Device: Dapivirine vaginal ring; Vaginal ring containing 25 mg of dapivirine; Drug: FTC/TDF; Tablet containing 200 mg FTC/300 mg TDF; Other Name: Emtricitabine/Tenofovir Disoproxil Fumarate; Truvada
Experimental: Sequence B: FTC/TDF + Dapivirine vaginal ring; Participants will receive one FTC/TDF oral tablet taken by mouth daily for 24 weeks, followed by one 25 mg dapivirine vaginal ring inserted vaginally each month for 24 weeks, followed by participant's choice of either or neither study product for 24 weeks.	Device: Dapivirine vaginal ring; Vaginal ring containing 25 mg of dapivirine; Drug: FTC/TDF; Tablet containing 200 mg FTC/300 mg TDF; Other Name: Emtricitabine/Tenofovir Disoproxil Fumarate; Truvada

Outcome Measures

Primary Outcome Measures :

1. Frequency of Grade 2 or higher adverse events (AEs) [ Time Frame: Measured through Week 24 ]
   As defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies [Dated November 2007])
2. Measurement of detectable drug levels in blood [ Time Frame: Measured through Week 24 ]
   Based on laboratory evaluations
3. Measurement of residual drug levels in returned VRs [ Time Frame: Measured through Week 24 ]
   Based on laboratory evaluations

Secondary Outcome Measures :

1. Percentage of participants reporting acceptability of study product [ Time Frame: Measured through Week 24 ]
   Based on participant report
2. Measurement of detectable drug levels in blood [ Time Frame: Measured through Week 72 ]
   Based on laboratory evaluations
3. Measurement of residual drug levels in returned VRs [ Time Frame: Measured through Week 72 ]
   Based on laboratory evaluations
4. Percentage of participants selecting dapivirine VR as compared to FTC/TDF oral tablets [ Time Frame: Measured through Week 72 ]
   Assessed by participant product selection during third product use period
5. Percentage of participants reporting preference for dapivirine VR as compared to FTC/TDF oral tablets [ Time Frame: Measured through Week 72 ]
   Assessed by participant report of product preference

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Age 16 through 21 years (inclusive) at Enrollment, verified per site standard operating procedures (SOPs).
• Able and willing to provide informed consent, and if under the legal age of consent be able to provide informed assent and obtain parental or guardian permission/consent, to be screened for and to enroll in MTN-034 (as specified in site SOP).
• Able and willing to provide adequate locator information, as defined in site SOPs.
• Able and willing to comply with all study procedural requirements.
• Per participant report at Screening, post-menarche.
• HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithms found in the study protocol).
• Per participant report at Screening, history of at least one episode of sexual intercourse in participant's lifetime.
• Negative pregnancy test at Screening and Enrollment.

• Per participant report, use of an effective method of contraception for at least two months prior to Enrollment, and intending to continue use of an effective method for the duration of study participation; effective methods include:

  • hormonal methods (except contraceptive ring).
  • intrauterine device (IUD).
  • Note: Participant must be on the same contraception method for at least the two months prior to Enrollment.

• Per participant report at Screening, willing to abstain from inserting anything into the vagina for 72 hours prior to each study visit, including receptive intercourse.

  • Note: In the event the VR has been expelled and requires reinsertion, repositioning the VR is permitted.
  • Note: Participant use of tampons is permitted at any time during the study.
• At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation, unless approved by the Protocol Safety Review Team (PSRT).

Exclusion Criteria:

• Per participant report at Screening and Enrollment, intends to do any of the following during the study participation period:

  • become pregnant.
  • access and/or use oral PrEP outside the context of study participation.
  • relocate away from the study site.
  • travel away from the study site for a time period that would interfere with product resupply and study participation.
• At Screening or Enrollment, has a positive HIV test.

• Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), sexually transmitted infection (STI) or reproductive tract infection (RTI) requiring treatment per World Health Organization (WHO) guidelines at Screening or Enrollment.

  • Note: Otherwise eligible participants diagnosed during screening with a UTI, PID or STI/RTI requiring treatment per WHO guidelines — other than asymptomatic bacterial vaginosis (BV) and asymptomatic candidiasis — are offered treatment consistent with WHO recommendations. If treatment is completed and symptoms have resolved within 70 days of obtaining informed assent/consent for screening, the participant may be enrolled. Genital warts requiring treatment also must be treated prior to enrollment. Genital warts requiring therapy are defined as those that cause undue burden or discomfort to the participant, including bulky size, unacceptable appearance, or physical discomfort.

• At Enrollment, has a clinically apparent Grade 2 or higher pelvic exam finding.

  • Note: Cervical friability bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the Investigator of Record (IoR)/designee is considered expected non-menstrual bleeding and is not exclusionary.
  • Note: Otherwise eligible participants with exclusionary pelvic exam findings may be enrolled/randomized after the findings have improved to a non-exclusionary severity grading or resolved. If improvement to a non-exclusionary grade or resolution is documented within 70 days of providing informed assent/consent for screening, the participant may be enrolled.

• Participant report and/or clinical evidence of any of the following:

  • Known adverse reaction to any of the study products (ever).
  • Known adverse reaction to latex and polyurethane (ever).
  • Symptoms suggestive of acute HIV infection at Screening or Enrollment.
  • Non-therapeutic injection drug use in the 12 months prior to Enrollment.
  • Use of HIV PEP and/or PrEP within the 3 months prior to Enrollment.
  • Currently breastfeeding.
  • Last pregnancy outcome within 8 weeks or less of Enrollment.
  • Participation in any other research study involving drugs, medical devices, vaginal products or vaccines within 60 days of Enrollment.
  • At Enrollment, as determined by the IoR/designee, has any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease.

• Has any of the following laboratory abnormalities at Screening Visit:

  • Positive for hepatitis B surface antigen (HBsAG).
  • Hemoglobin Grade 2 or higher.

  • Calculated creatinine clearance less than 60 mL/min by the Schwartz Equation.

    • Note: Otherwise eligible participants with an exclusionary test may be re-tested during the screening process; re-testing procedure details can be found in the MTN-034 Study Specific Procedures (SSP) Manual. If improvement to a non-exclusionary grade or resolution is documented within 70 days of providing informed assent/consent for screening, the participant may be enrolled.
• Has any other condition that, in the opinion of the IoR/designee, would preclude informed assent/consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Contacts and Locations

Locations

Kenya

Kisumu Crs; Withdrawn

Kisumu, Nyanza, Kenya, 40100

South Africa

Wits Reproductive Health and HIV Institute CRS (WRHI CRS); Recruiting

Johannesburg, Gauteng, South Africa, 2038

Contact: Thesla Palanee, MMED, Ph.D. 27-11-3585471 tpalanee@wrhi.ac.za

Emavundleni CRS; Recruiting

Cape Town, Western Cape, South Africa, 7750

Contact: Elaine Sebastian 27-21-6505848 elaine.sebastian@hiv-research.org.za

Uganda

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS; Recruiting

Kampala, Uganda

Contact: Carolyne P. Onyango, MB ChB, M.S. 256-414-541044 carolonyango@mujhu.org

Zimbabwe

Spilhaus CRS; Recruiting

Southerton, Harare, Zimbabwe

Contact: Eunice Tahuringana, B.A., RGN 263-772-882704 etahuringana@uzchs-ctrc.org

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Gonasagrie Nair, MBChB, MPH; Emavundleni Research Centre

More Information

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03593655
• Other Study ID Numbers: MTN-034; 12066 ( Registry Identifier: DAIDS-ES Registry Number )
• First Posted: July 20, 2018
• Last Update Posted: November 5, 2019
• Last Verified: November 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Tenofovir; Emtricitabine; Dapivirine; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Anti-HIV Agents